Focus on ischaemic heart disease: from mechanisms to prevention and treatment

For the podcast associated with this article, please visit https://academic.oup.com/eurheartj/pages/Podcasts. This Focus Issue on ischaemic heart disease contains a contribution entitled ‘Great Debate: computed tomography coronary angiography should be the initial diagnostic test in suspected angina’ by experts in the field and coordinated by Professor Colin Berry.1 Should clinicians adopt a default anatomical strategy or a more individualized approach? The anatomical approach using computed tomography coronary angiography (CTCA) is generating growing interest2 and is commended in the UK National Institute for Health and Care Excellence clinical guideline. Personalized medicine takes account of the patient’s characteristics to stratify management, and this approach is endorsed in the more recent clinical guidelines from the European Society of Cardiology and in North American guidelines. The Editors of the European Heart Journal have posed the motion: ‘CTCA should be the initial diagnostic test in suspected angina’. Kramer and colleagues write for the motion and Professor Kunadian and colleagues write against it. We hope you agree that the authors have captured the key issues. Cardiac involvement of Erdheim–Chester disease (ECD), a rare L group histiocytosis, has been reported to be associated with poor outcomes, but systematic studies are lacking. In a Clinical Research article entitled ‘Prevalence, patterns, and outcomes of cardiac involvement in Erdheim–Chester disease’, Lévi-Dan Azoulay from the Assistance Publique-Hôpitaux de Paris in France, and colleagues aimed to investigate the prevalence, clinical features, imaging features, and prognosis of cardiac involvement in ECD in a large series.3 All patients with ECD who underwent cardiac magnetic resonance (CMR) imaging between 2003 and 2019 at a French tertiary centre were retrospectively included. Primary outcome was all-cause mortality. Secondary outcomes were pericarditis, cardiac tamponade, conduction disorders, device implantation, and coronary artery disease (CAD). A total of 200 patients were included (mean age 63 years, 30% female, 58% BRAFV600E mutated). Median follow-up was 5.5 years. On CMR, right atrioventricular sulcus infiltration was observed in 37% of patients, and pericardial effusion was seen in 24% of patients. In total, 8 patients (4%) had pericarditis (7 acute, 1 constrictive), 10 patients (5%) had cardiac tamponade, 5 patients (2.5%) had ECD-related high-degree conduction disorders, and 45 patients (23%) had CAD. Overall, cardiac involvement was present in 96 patients (48%) and was associated with BRAFV600E mutation [odds ratio (OR) = 7.4, P < 0.001] and ECD-related clinical events (OR = 5, P = 0.004) but not with lower survival in multivariate analysis [adjusted hazard ratio (HR) = 1.4, P = 0.2] (Figure 1). More than half of ECD patients had evidence of cardiac involvement on CMR, which was associated with a higher risk of clinical events. Abbreviations: CMR, cardiac magnetic resonance; ECD, Erdheim–Chester disease; HR, hazard ratio; OR, odds ratio.3 Cardiac involvement is present in nearly half of ECD patients and is associated with BRAFV600E mutation and complications (pericarditis, cardiac tamponade, and conduction disorders) but not with lower survival. This manuscript is accompanied by an Editorial by Matthew Collin from Newcastle University in the UK.4 Dr Collin concludes that caring for patients with ECD is by nature a multidisciplinary activity, and engagement with cardiologists is essential to investigate and manage cardiac involvement optimally. A patient-led organization, the ECD Global Alliance, has been critical in raising awareness over the last few years, and has many resources for patients and clinicians interested in learning more. While the beneficial effects of moderate exercise are beyond any reasonable doubt, those of endurance exercise are more controversial.5 In a Clinical Research article entitled ‘Lifelong endurance exercise and its relation with coronary atherosclerosis’ Ruben De Bosscher from KU Leuven in Belgium, and colleagues enrolled 191 lifelong master endurance athletes, 191 late-onset athletes (endurance sports initiation after 30 years of age), and 176 healthy non-athletes, all male with a low cardiovascular risk profile.6 Peak oxygen uptake quantified fitness. The primary endpoint was the prevalence of coronary plaques (calcified, mixed, and non-calcified) on CTCA. Analyses were corrected for multiple cardiovascular risk factors. The median age was 55 years in all groups. Lifelong and late-onset athletes had higher peak oxygen uptake than non-athletes. Lifelong endurance sport was associated with having ≥1 coronary plaque (OR 1.86), ≥ 1 proximal plaque (OR 1.96), ≥ 1 calcified plaques (OR 1.58), ≥ 1 calcified proximal plaque (OR 2.07, ), ≥ 1 non-calcified plaque (OR 1.95), ≥ 1 non-calcified proximal plaque (OR 2.80), and ≥1 mixed plaque (OR 1.78) as compared with a healthy non-athletic lifestyle (Figure 2). The Master@Heart study compared the prevalence of calcified, mixed, and non-calcified coronary plaques by computed tomography between 176 controls, 191 late-onset endurance athletes, and 191 lifelong endurance athletes, in the absence of established risk factors for coronary artery disease. Lifelong endurance athletes had the highest coronary plaque burden regardless of plaque types.6 The authors conclude that lifelong endurance sport participation is not associated with a more favourable coronary plaque composition compared with a healthy lifestyle. Indeed, lifelong endurance athletes have more coronary plaques, including more non-calcified plaques in proximal segments, than fit and healthy individuals with a similarly low cardiovascular risk profile. The contribution is accompanied by an Editorial by Saad Fyyaz and Michael Papadakis from the University of London, UK.7 The authors highlight that this is a well-designed study which adds to an intriguing body of research demonstrating that athletes engaging in lifelong endurance exercise are more likely to exhibit elevated coronary artery calcification scores. It also questions the favourable plaque profile suggested by others. Longitudinal studies are required to understand the significance of these findings. The challenge remains the low event rates, further compounded amongst female cohorts who demonstrate less coronary disease, highlighting the need for multicentre studies of large cohorts. The best evidence to date remains that exercise has an overwhelmingly positive influence extending beyond the cardiovascular system. The high intensity/volume exercise and the associated lifestyle of elite endurance athletes confers significant benefits, with athletes gaining an average of 5–7 years of life compared with sedentary individuals. As such, clinicians should continue to encourage exercise and address all traditional cardiovascular risk factors. Whether extremes of exercise pose a detrimental effect remains to be proven. Air pollution has a remarkably negative impact on cardiovascular diseases.8–12 Data on the impact of air pollution on the pathobiology of coronary instability, however, are still limited. In a Rapid Communications article entitled ‘Air pollution and plaque healing in acute coronary syndromes’, Michele Russo from the Catholic University of the Sacred Heart in Rome, Italy, and colleagues note that plaque healing plays a key role in coronary atherosclerosis and represents ‘the second hit’ required to cause an acute coronary syndrome (ACS) after plaque disruption, this latter being the ‘first hit’.13 Moreover, an impaired plaque healing has been found in patients with recurrent ACS, suggesting its importance in preventing repeated symptomatic coronary thrombosis. The authors investigated the association between air pollution and healed plaques in patients with ACS, stratified by first or recurrent ACS. They enrolled 133 ACS patients. Healed plaques were found in the culprit lesion of 11 (38%) patients with recurrent ACS and of 44 (42%) patients with first ACS. Among patients with recurrent ACS, those with healed plaques, compared with those without, had lower PM2.5 exposure levels (P = 0.026), and PM2.5 was the only variable associated with healed plaque (P = 0.048). Among patients with first ACS, there were no significant differences in PM2.5 exposure levels between patients with and without healed plaques. The authors conclude that the study shows for the first time that, among patients with recurrent ACS, a higher long-term PM2.5 exposure is associated with an impaired plaque healing along with the presence of more vulnerable plaque features at the culprit lesion. The issue also contains another Rapid Communications article entitled ‘Radial artery vs. internal thoracic artery or saphenous vein grafts: 15-year results of the RAPCO trials’ by Garry Hamilton from the University of Melbourne, Australia, and colleagues. The standard coronary artery bypass graft (CABG) operation uses the left internal thoracic artery to the left anterior descending artery (LITA–LAD). However, the optimal graft for the second most important coronary target remains debated.14–16 The Radial Artery Patency and Clinical Outcomes (RAPCO) programme was designed as two separate randomized trials in which the radial artery (RA) was compared with either the right internal thoracic artery (RAPCO-RITA)—as a free graft—or the saphenous vein (RAPCO-SV), as the conduit for grafting the second most important coronary target. The authors herein present the 15-year clinical outcomes of the RAPCO programme. The endpoint was a composite of major cardiovascular events (MACE) including all-cause death, myocardial infarction, or repeat revascularization. The 15-year MACE rate was 39% in the RA group and 48.5% in the RITA group (HR 0.74, P = 0.04). In the RAPCO-SV trial, the 15-year MACE rate was 60.2% in the RA group and 73.2% in the SV group (HR 0.71, P = 0.04). The authors conclude that using the RA to graft the second most important coronary target, in patients undergoing coronary surgery, improves long-term clinical outcomes compared with either the free RITA or the SV. This suggests that the RA should be favoured to complement the LITA–LAD graft unless there is a specific contraindication. The issue also contains two Discussion Forum contributions. In a commentary entitled ‘Diverging opinions for high bleeding risk patients’, Ahmet Anıl Baskurt from the Dokuz Eylul University School of Medicine in Izmir, Turkey comments on the recent ‘2022 ESC Guidelines on cardiovascular assessment and management of patients undergoing non-cardiac surgery’.17,18 Sigrun Halvorsen, Julinda Mehilli, and Tobias Geisler respond in a separate comment.19 The editors hope that this issue of the European Heart Journal will be of interest to its readers. Dr. Crea reports speaker fees from Abbott, Amgen, Astra Zeneca, BMS, Chiesi, Daiichi Sankyo, Menarini outside the submitted work. With thanks to Amelia Meier-Batschelet, Johanna Huggler, and Martin Meyer for help with compilation of this article.